Stilbenes based compounds are immensely important in the field of medicines and hydroxylated stilbenes have been found in a multitude of medicinal plants. (J. C. Roberts, J. A. Pincock, J. Org. Chem., 2006, 71, 1480) For example, resveratrol, a hydroxylated stilbene, present in grapes and other fruits (J. Burns, T. Yokota, H. Ashihara, M. E. J. Lean, A. J. Crozier, J. Agric. Food Chem., 2002, 50, 3337; G. J. Soleas, E. P. Diamandis, D. M. Goldberg, Clin. Biochem., 1997, 30, 91) have been reported to play a role in the prevention of heart diseases associated with red wine consumption because of its properties of platelet aggregation (C. R. Pace-Asciak, S. Hahn, E. P. Diamandis, G. Soleas, D. M. Goldberg, Clin. Chem. Acta., 1995, 235, 207); eicosanoid synthesis alteration (Y. Kimura, H. Okuda, S. Arichi, Biochim. Biophys. Acta., 1985, 834, 275), lipid and lipoprotein metabolism modulation (L. Belguendouz, L. Fremont, M. T. Gozzellino, Biochem. Pharmacol., 1998, 55, 811; E. N. Frankel, A. L. Waterhouse, J. E. Kinsella, Lancet., 1993, 341, 1103). Similarly, other hydroxy substituted stilbenes also have profound applications in the medicinal field (A. M. Rimando, M. Cuendet, C. Desmarchelier, R. G. Mehta, J. M. Pezzuto, S. O. Duke, J. Agric. Chem., 2002, 50, 3453). Similarly, styrene based compounds of natural origin have received tremendous thrust from chemists all over the world due to a plethora of its applications in different spheres of services to mankind such as to flavour and fragrance industries, pharmaceutical sector etc. Compounds like substituted 4-vinylphenols such as 4-vinylguaiacol (p-vinylguaiacol or 2-methoxy-4-vinylphenol or 4-hydroxy-3-methoxystyrene or 4-ethenyl-2-methoxyphenol), 4-hydroxystyrene (p-vinylphenol or 4-ethenylphenol), 3,5-dimethoxy-4-hydroxy styrene and others have been the most extensively investigated ones due to their widespread application in food and alcoholic beverages, flavouring substances and as intermediates in the preparation of polymers and co-polymers useful in coatings, electronic applications, ion exchange resins and photo resists etc. (Perfume and Flavor Chemicals, Aroma Chemicals, ed. A. Steffen, Allured Publishing Corporation, 1994, Vol I-IV and Encyclopedia of Food and Color Additives, ed. A. B. George, CRC Press, Inc., 1996, Vol I-II).
The preparation of these substituted 2- or 4-hydroxy stilbene or styrene derivatives such as combretastatin A-4, reserveratrol, 4-vinylguaiacol (FEMA GRAS No. 2675), 4-vinylphenol (FEMA GRAS No. 3739) and others are well known in the art. However, a more efficient process for preparing 2- or 4-hydroxyl substituted arylethenes is desired. The present invention, which is an extension of our previous patent (U.S. Pat. No. 6,989,467, 2006), provides a process wherein microwave assisted (A. K. Bose, B. K. Banik, N. Lavlinskaia, M. Jayaraman, M. S. Manhas, Chemtech., 1997, 27, 18; M. Larhed, Hallberg, Drug Discovery Today., 2001, 6(8), 406,) decarboxylation of 2- or 4-hydroxy substituted cinnamic acids and their derivatives in the presence of a base, solid support with or without a solvent to provide corresponding substituted 2- or 4-hydroxy arylethenes in one pot. The following prior art references are disclosed:    U.S. Pat. No. 6,468,566 discloses a method for decarboxylation of ferulic acid with decarboxylase enzyme.    U.S. Pat. No. 6,235,507 discloses a method for decarboxylation of ferulic acid from microbial conversion at a pH more than 9.    U.S. Pat. No. 5,493,062 discloses a method for the preparation of styrenes from deamination of the corresponding aminoethylphenol (AEP) at high temperature.    U.S. Pat. No. 5,087,772 discloses a method for the preparation of styrenes from deacetoxylation of the corresponding acetoxystyrene with a suitable alcohol in the presence of a suitable base.    U.S. Pat. No. 20040147788 discloses a method for the synthesis of stilbene derivatives through Wittig reaction.    U.S. Pat. No. 20040015020 A1 discloses a method for the synthesis of E-isomer of stilbene through halide assisted conversion of corresponding Z-isomer.    Journal of Biotechnology, 2000, 80, 195; discloses a method for the preparation of 4-vinylguaiacol from decarboxylation of ferulic acid by Bacillus coagulants.     Enzyme and Microbial Technology, 1998, 23, 261; discloses a method for the decarboxylation of ferulic acid by Bacillus pumilus.     Archives of Biochemistry and Biophysics, 1998, 359(2), 225; discloses a method for the decarboxylation of hydroxycinnamic acid by Klebsiella oxytoca.     J. Biol. Chem., 1993, 268, 23954; discloses a method for decarboxylation of cinnamic acid by Rhodotorula rubra.     Appl. Environ. Microbial., 1993, 59, 2244; discloses a method for the decarboxylation of ferulic acid by Saccharomyces cerevisiae and Pseudomonas fluorescens.     J. Biol. Chem., 1962, 237, 2926; discloses a method for the decarboxylation of 4-hydroxy-cinnamic acid by Aerobacter.    Tetrahedron., 2004, 60, 5563; discloses a method for the synthesis of resveratrol and their analogues through Heck reaction in organic and aqueous solvents.    Journal of Med. Chem., 2002, 45, 2534; discloses a method for the synthesis of hydroxy stilbenes and benzophenones through Wittig reaction.    J. Biol. Chem., 1961, 236, 2302; discloses a method for the decarboxylation of trans-cinnamic acids into styrene derivatives by using pyruvate decarboxylase enzyme.    J. Biol. Chem., 1957, 227, 151; discloses a method for the decarboxylation of trans-cinnamic acids into styrene derivatives by using oxalate decarboxylase enzyme.    J. Biol. Chem., 1960, 235, 1649; discloses a method for the decarboxylation of trans-cinnamic acids into styrene derivatives by using glutamate decarboxylase enzyme.    J. Biol. Chem., 1957, 226, 703; discloses a method for the decarboxylation of trans-cinnamic acids into styrene derivatives by using aconitate decarboxylase enzyme.    J. Biol. Chem., 1964, 239, 879; discloses a method for the decarboxylation of trans-cinnamic acids into styrene derivatives by using aspartate 4-decarboxylase enzyme.    Natural Product Research., 2006, 20, 247, discloses a method for the improve synthesis of resveratrol through two step process Wittig reaction and Heck coupling.    Synthesis, 2006, 273, discloses a method for the synthesis of biologically important trans-stilbenes via Ru-catalyzed cross metathesis.    J. Med. Chem., 2005, 48, 6783, discloses a method for the synthesis resveratrol analogue with high ceramide-mediated proapoptotic activity on human breast cancer cells.    Carbohydrate Research., 1997, 301, 95; discloses a method for the synthesis of various hydroxy stilbenes and their glycosides through Wittig reaction.    Tetrahedron Lett., 1999, 40, 6595; discloses a method for the decarboxylation of trans-cinnamic acids into styrene derivatives by using plant cell cultures.    J. Biol. Chem., 1962, 237, 2926; discloses a method for the decarboxylation of trans-4-hydroxycinnamic acid into 4-hydroxystyrene.    Applied Catalyst A: General, 1995, 133, 219; discloses a method for the preparation of styrene from dehydrogenation of ethylbenzene.    Organic Synthesis Collective Volume 1, 1941, 441-442 as well as Volume IV, 1963, 731-734; disclose a method for the preparation of styrenes by decarboxylation of cinnamic acids with quinoline in the presence of copper powder at 200-300° C.
Some of other typical prior art references include U.S. Pat. Nos. 4,316,995; 4,868,256; 4,868,257; 4,933,495; 5,072,025; 5,128,253; 5,247,124; 5,344,963; 5,563,289; 6,111,133; European Pat. Nos. 0-128-984; 0-108-624; Dutch Pat. Nos. 72.09426; 72.13842; 75.04532; Japan Pat. Nos. 10306126; 6049137; J. Am. Chem. Soc., 1948, 70, 2295; J. Am. Chem. Soc., 1950, 72, 5198; J. Am. Chem. Soc., 1958, 80, 3645; J. Org. Chem., 1958, 23, 544; Chem. Berichte, 1959, 92, 2958; Tetrahedron, 1975, 31, 235; Can. J. Chem., 1985, 63, 153. Although, the above methods have been proven to be useful, they suffer from one or more process deficiencies. For example, in some instances processes of this type necessarily involve resorting to sub-ambient temperatures and in some others, the substrates require designing of multi-step processes which of course, involve some considerable process control and leads to overall poor yield of the products.
Natural plant products represent one of the important branches of organic chemistry which serves mankind to satiate his wide range of necessities for food, perfumery, and pharmaceutical industries etc. Naturally occurring non-nutritive agents such as flavonoids, phenolic compounds, styrenes, stilbenes and many others are believed to possess varied pharmacological activities (S. M. Kau, Oncogenesis, 1997, 8, 47) whose clinical relevance is dependent on extrapolation from epidemiological data. For example, hydroxylated stilbenes, a class of phenolic compounds, includes one of the most important therapeutic agents like combretastatin A-4, pterostilbene and resveratrol for the prevention of fatal diseases like cancer and heart diseases. Combretastatin A-4, isolated from the African bush willow, Combretum caffrum shows exciting potential as an anti-cancer agent, binding strongly to tubulin and displaying potent and selective toxicity towards tumor vasculature (U.S. Pat. No. 4996; Brit. J. Cancer, 1999, 81, 1318; Brit. J. Cancer, 1995, 71, 705). Combretastatin A-4 is able to elicit irreversible vascular shutdown within solid tumors, leaving normal vasculature intact (E. Hamel, C. M. Lin, Biochem. Pharmacol., 1983, 32, 3863; D. J. Chaplin, G. R. Pettit, C. S. Parkins, S. A. Hill, Brit. J. Cancer, 1996, 74, S86; G. G. Dark, S. A. Hill, V. E. Prise, G. M. Tozer, G. R. Pettit, D. J. Chaplin, Cancer Res. 1997, 57, 1829). Similarly, resveratrol, a natural molecule, occuring in a narrow range of spermatophytes, including vines, peanuts and pine trees, is known to prevent heart disease. The compound is shown to be bioactive (C. A. De La Lastra, I. Villegas, Molecular Nutrition and Food chemistry, 2005, 49, 405; S. H. Inayat-Hussain, N. F. Thomas, Expert Opin. Ther. Pat., 2004, 14, 819; F. Wolter, J. Stein, Drugs Future, 2002, 27, 949; Y. Kimura, H. Okuda, S. Arichi, Biochim. Biophys. Acta, 1985, 834, 275; L. A. Stivala, M. Savio, F. Carafoli, P. Perucca, L. Bianchi, G. Maga, L. Forti, U. M. Pagoni, A. Albini., E. Prosperi, V. Vannini, J. Boil. Chem., 2001, 176, 22586; Y. Schneider, B. Duranton, F. Gossé, R. Schleiffer, N. Seiler, F. Raul, Nutr. Cancer, 2001, 39, 102; M. Chung, C. Teng, K. Cheng, F. Ko, C. Lin, Planta Med., 1992, 58, 274; Y. Inamori, M. Kubo, H. Tsujibo, M. Ogawa, Y. Saito, Y. Miki, S. Takemura, Chem. Pharm. Bull., 1987, 35, 887). Its synthesis in the plants is induced by stress, including infection or UV-irradiation. High concentrations of this compound have been isolated from the plant Poligonum cuspidatum. Resveratrol is shown to inhibit synthesis of thromboxnae in platelets and leukotrienes in neutrophils, and modulate the synthesis and secretion of lipoproteins in animals and human cell lines and thus, significantly prevent coronary diseases. Moreover, resveratrol prevents chemical induction of preneoplastic lesion in a mouse mammary gland culture model and can slowdown the growth of skin tumors. It is shown that resveratrol can protect against a variety of diseases associated with AhR ligand. Hence, resveratrol acts as AhR antagonist and thus helps preventing cancer and viral infections such as AIDS (K. W. Bock, Physiol, Biochem. Pharmacol., 1994, 125, 1; J.-F. Savouret, M. Antenos, M. Quesne, J. Xu, E. Milgrom, R. F. Casper, J. Boil. Chem., 2001, 276, 3054; M. Poirot, P. De Medina, F. Delarue, J. J. Perie, A. Klaebe, J. C. Faye, Bioorg. Med. Chem., 2000, 8, 2007). This compound is also known to possess anti-inflammatory and anti-mutagebnic activities. (Science, 1995, 267, 1782; Science, 1997, 275, 218). Similarly, natural vinylphenols, another class of important styrene derivatives, are immensely important constituents for aroma and flavor industries and are found in a variety of plant products. For example, vinylguaiacol (FEMA GRAS NO. 2675) is obtained from the pods of Hibiscus esculentus (okra) and Digitaria exilis and also found in cooked apple, grape fruit juice (Citrus paradisi), feijoa fruit (Feijoa sellowiana), Vitis vinifera, strawberry fruit, raw asparagus, leaves and stalks of celery, crispbread, white wine, red wine, coffee, partially fermented tea, roasted peanuts (Arachis hypogea), raw beans, red sage (Taxus sage) and other natural sources (M. A. Jennifer, M. Glesni, Phytochemistry, 1990, 29 (4), 1201; P. Hanna, N. Michael, Z. Uri, L. R. Russell, N. J. Steven, J. Agric. Food Chem., 1992, 40, 764; O. O. Lasekan, J. P. F. Teixeira, T. J. G. Salva, Food Chemistry, 2001, 75, 333). 4-vinylguiacol is also found as one of the most odour active compounds in roasted white sesame seeds which are widely used as a flavouring material in food stuffs. (Progress In Flavour Precursor Studies, ed. P. Schreier, P. Winterhalter, Allured Publishing Corporation, USA, 1993, 343-360; W. Toshiro, Y. Akira, N. Shiro, T. J. Shigero, J. Chromatogra. A, 1998, 3, 409). On the same lines, 4-vinylphenol, also known as 4-hydroxystyrene, (FEMA GRAS NO. 3739) is found in cooked apple, black currants (buds), raw asparagus, tomato, cognac, white wine, red wine, rose wine, coffee, green tea, partially fermented tea, microbial fermented tea, heated soyabean, Boletus edulis, coriander seed (Coriandrum sativum), oil of vetiver (Vetiveria zizamioides), olive oil and other natural sources (S. Souleymane, C. Jean, Phytochemistry, 1973, 2925; S. Takayuki, N. Osamu, Phytochemistry, 1982, 1(3), 793; O. Makoto, W. Kazumasa, N. Haruki, Y. Kiyoyuki, Tetrahedron, 1987, 43(22), 5275; J. J. S. Saez, M. D. H. Garraleta, T. B. Otero, Analytica Chimica Acta, 1991, 247(2), 295; F. Vicente, L. Ricardo, E. Ana, F. C. Juan, J. Chromatogar. A, 1998, 806, 349; J. W. Nicholas, N. Arjan, B. F. Craig, W. Gray, Current Opinion in Biotechnology, 2000, 11, 490; P. Rainer, S. Alexander, P. Horst, FEMS Microbiology Letters, 2001, 205, 9; L. Ricardo, A. Margarita, C. Juan, F. Vicente, J. Chromatogra. A, 2002, 966, 167; K. Kuroda, D. R. Dimmel, J. Analytical and Applied Pyrolysis, 2002, 62, 259; K. Kuroda, A. Izumi, B. B. Mazumder, Y. Ohtani, K. Sameshima, J. Analytical and Applied Pyrolysis, 2002, 64, 453; F. Daniel, V. Ivano, E. S. Colin, J. Chromatogra. A, 2002, 967, 235). In addition to the above mentioned vinylphenols, there are several other styrenes which are found in different plants and are known for various applications. (F. Nagashima, Y. Murakami, Y. Asakawa, Phytochemistry, 1999, 51, 1101). Beside, vinylphenols are also known to possess a wide range of biological activities including antibacterial, antifungal and hypolipidemic activities etc. (A. A. William, J. M. David, C. Priyotosh, Phytochemistry, 1996, 42(5), 1321; C. Adriana, G. Leticia, S. Maria, M. Elizdath, A. J. Hugo, D. Francisco, C. Germán, T. Joaquin, F. Arzneim, Drug Res., 2001, 51(II), 535). In addition to above, vinylphenols and related styrenes are also found as versatile intermediates for a wide range of products (R. R. Stuart, S. M. Colette, J. L. David, Biorganic & Medicinal Chemistry, 1994, 2(6), 553; M. Atsushi, K. Takeo, I. Yoshinobu, Reactive & Functional Polymers, 1998, 37, 39; C. B. Michel, L. M. Adriano, T. Igor, J. of Molecular Catalyst A: Chemical, 1999, 143, 131; J. C. Pedro, G. Bárbara, A. R. Miguel, Tetrahedron Lett; 2000, 41, 979).
In the pretext of above discussion, 2- or 4-hydroxy substituted arylethenes like stilbenes and styrenes can unhesitatingly be counted as greatly valued to humankind and as a consequence, a lot of synthetic methods are reported for their synthesis. In case of synthesis of stilbene derivatives, the reported methods involve Wittig type and modified Julia olefination, reaction of benzyllithium with benzaldehydes followed by dehydration, Perkins reaction, cross metathesis of styrenes, Suzuki reaction with B-halostyrenes, decarbonylative Heck reaction between acid chloride and styrene and palladium catalysed arylation of styrenes with halobenzene (G. R. Pettit, M. P. Grealish, M. K. Jung, E. Hamel, R. K. Pettit, J.-C. Chapuis, J. M. Schmidt, J. Med. Chem., 2002, 45, 2534; M. Roberti, D. Pizzirani, D. Simony, R. Rondanin, R. Baruchello, C. Bonora, F. Buscemi, S. Grimaudo, M. Tolomeo, J. Med. Chem., 2003, 46, 3546; H. Meier, U. Dullweber, Tetrahedron Lett., 1996, 37, 1191; J. Yu, M. J. Gaunt, J. B. Spencer, J. Org. Chem., 2002, 67, 4627; D. A. Alonso, C. Nájera, M. Varea, Tetrahedron Lett., 2004, 45, 573; E. Alonso, D. J. Ramón, M. Yus, J. Org. Chem., 1997, 62, 47; G. Solladié, Y. Pasturel-Jacopé, J. Maignun, Tetrahedron, 2003, 59, 3315; S. Chang, Y. Na, H. J. Shin, E. Choi, L. S. Jeong, Tetrahedron Lett., 2002, 43, 7445; S. Eddarir, Z. Abdelhadi, C. Rolando, Tetrahedron Lett., 2001, 42, 9127; M. B. Andrus, J. Liu, E. L. Meredith, E. Nartey, Tetrahedron Lett., 2003, 44, 4819; T. Jeffery, B. Ferber, Tetrahedron Lett., 2003, 44, 193; N. F. Thomas, K. C. Lee, T. Paraidathathu, J. F. F. Weber, K. Awing, Tetrahedron Lett., 2002, 43, 3151). Similarly, reported methods for the synthesis of vinyl phenols include decarboxylation of trans-cinnamic acids which is carried out by heating the cinnamic acids under reflux at 200-300° C. for several hours in quinoline in the presence of copper powder (Organic Synthesis Collective Volume I, 1941, 441-442 and Volume IV, 1963, 731-734; A. S. Robert, R. D. Charles, A. P. Leo, Tertrahedron Lett., 1976, 49, 4447). Similarly, catalytic oxidation of 1,1-diphenylethane (1,1-di-(4-hydroxyphenyl)ethane) provides styrene (i.e. 4-hydroxy-3-methoxystyrene) (Perfume and Flavor Chemicals (Aroma Chemicals), ed. Steffen, A., Allured Publishing Corporation, 1994, Vol II, 1891). In addition to chemical methods, several microbial transformations are also reported for the preparation of styrenes especially substituted vinylphenols (T. Masumi, A. Kazuo, Tetrahedron Lett., 1999, 40, 6595; and Encyclopedia of Food and Color Additives, ed. George, A. B., CRC Press, Inc., Vol II, 1996, 705). All the above methods have various limitations, for example, low yield, use of expensive reagents and formation of unwanted side products.
It is therefore, becomes an object of the invention to provide rapid and economical process for the preparation of 2- or 4-hydroxy substituted arylethenes from commercially available 2- or 4-hydroxy substituted cinnamic acids and their derivatives as well as to eliminate the disadvantages associated with the above patents and papers.
In conclusion, our invention discloses a simple and economical process for preparing 2- or 4-hydroxy substituted arylethenes from economical material 2- or 4-hydroxy substituted cinnamic acids and their derivatives in the presence of a base, solid support with or without solvent under microwave or conventional condition. Other objectives and advantages of the present invention will be apparent as the description progresses.